Flashcards in Week 3 Deck (131)
In autosomal dominant disorders, for related, unaffected individuals (no info on parents available), you cannot determine genotype without test
TRUE OR FALSE
In autosomal dominant disorders, for unrelated individuals (married in), you cannot assume that they are homozygous normal
TRUE OR FALSE
FALSE - you can UNLESS dz frequency is over 1/20
In FH, what is the chance that individuals are non-penetrant heterozygotes?
In autosomal dominant disorders, you can assume that affected individuals are heterozygotes unless what? (2)
- both parents affected
- dz frequency >1/20
In autosomal dominant disorders, disease frequency is equal to?
2q (heterozygote frequency)
In autosomal recessive disorders, disease frequency is equal to?
In autosomal recessive disorders, carrier frequency is equal to?
In an autosomal recessive disorder, if there are NO affected individuals in a sibship and you know that at least ONE of parents is a carrier, what is the probability that an UNAFFECTED child is a carrier?
In an autosomal recessive disorder, if there ARE affected individuals in a sibship OR you know that BOTH of the parents are carriers, the probability that an UNAFFECTED child is a carrier is?
In an autosomal recessive disorder, if one parent is homozygous affected and you do not know the carrier status of the UNAFFECTED, UNRELATED spouse, probability of an AFFECTED child is
1/2X the carrier frequency (= q)
When should you recommend carrier testing to an unaffected, unrelated spouse?
When other parent is homozygous affected or if they are a known carrier
In autosomal recessive disorders, affected individuals are often compound heterozygotes unless what?
There is cosanguinity
What protein is affected in cystic fibrosis?
cystic fibrosis transmembrane regulator (chloride channel in lungs and pancreas)
OCA1 is caused by what defect in the phenylalanine metabolism pathway?
Dopamine --> Melanin (catalyzed by tyrosinase)
How common is OCA1?
1/40K are affected, 1/100 are carrier
How does calcium get into the cell to raise cytosolic levels in
- nerve cell
- regular cell
- cardiac muscle cell
1) signal depolarizes PM --> ca++ channels open
2) signal activates receptor --> PLCB stimulated via Gq protein --> Ip3 produced --> Ca++ released from ER
3) Signal depolarizes cell and voltage gated channels open
Describe how foot odor is detected (6 steps)
1) Odorant binds to GPCR on olf neurons
2) Activates Golf protein (GDP-->GTP)
3) Alpha subunit activates adenylyl cyclase
4) cAMP produced
5) cAMP opens Na+ channels
6) Na+ influx into cell
Describe how the eye works in response to light
Rhodopsin is activated which activates Gt which increases PDE which decreases cGMP. Na+ channels close so cell is repolarized.
Describe how the eye works in response to dark
Rhodopsin is inactivated which inactivates Gt which decreases PDE which increases cGMP - Na++ channels open so the cell is depolarized
In GPCR densitization, activated GPCR sitmulates Grk to phosphorylate GPCR on multiple sites. This ATP-driven reaction allows what to bind and densitize the GPCR?
What are the five classes of NZ linked receptors
1) receptor tyrosine kinase (RTKs)
2) RTK assoc receptors
3) receptor like protein tyrosie phosphatases
5) receptor ser/threonine kinases
Epidermal growth factor, insulin, nerve growth factor, platelet derived growth factor, MCSF, fibroblast growth factors, ephrins, and vascular endothelial growth factors all act via ___________________
receptor tyrosine kinases
How do ligands induce dimerization? (3 ways)
1) ligand is a dimer with each subunit containing one receptor binding domain
2) monomeric signaling protein forms multimers by binding to heparin sulfate proteoglycans to crosslink its receptor
3) in contact dependent signaling, clusters formed in PM of signaling cell and then crosslink the receptors on target cell
Dimerization and autophosphorylation of receptor tyrosine kinases has what two effects?
1) phosphorylation @ some tyrosines promotes complete activation of kinase domains
2) phosphorylation @ tyrosines in other parts of receptor generates dockig sites for intracellular proteins --> form complexes that broadcast signals
PI3-kinase makes ______________ in the plasma membrane which are required for several signaling pathways
PIP2 and PIP3
______ inactivates Ras pathways while ______ activates Ras pathways
PLC-y produces _______ and _______
Describe a generic Ras-MAPK pathway
4) Activated Ras recruits MAPKKK (raf) to PM and activates it*
5) Ras recruits MAPKK (mek) to PM and activates it*
6) Ras activates MAPK (erk) *
7) Erk phosphorylates proteins, protein kinases, transcription regulators etc to cause changes in cell behavior*
* ATP catalyzed
What is the major function of PI3 kinase?
Stimulate cell growth